Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex

被引：21

作者：

AbuKhader, M

Heap, J

De Matteis, C

Kellam, B

Doughty, SW

Minton, N

Paoli, M

机构：

[1] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England

[2] Univ Nottingham, Inst Infect Immunity & Inflammat, Ctr Biomol Sci, Nottingham NG7 2RD, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 24期

关键词：

D O I：

10.1021/jm050730n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 angstrom resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.

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页码：7714 / 7719

页数：6

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